First genome-wide association study investigating blood pressure and renal traits in domestic cats.

Hypertension (HTN) and chronic kidney disease (CKD) are common in ageing cats. In humans, blood pressure (BP) and renal function are complex heritable traits. We performed the first feline genome-wide association study (GWAS) of quantitative traits systolic BP and creatinine and binary outcomes HTN and CKD, testing 1022 domestic cats with a discovery, replication and meta-analysis design. No variants reached experimental significance level in the discovery stage for any phenotype. Follow up of the top 9 variants for creatinine and 5 for systolic BP, one SNP reached experimental-wide significance for association with creatinine in the combined meta-analysis (chrD1.10258177; P = 1.34 × 10-6). Exploratory genetic risk score (GRS) analyses were performed. Within the discovery sample, GRS of top SNPs from the BP and creatinine GWAS show strong association with HTN and CKD but did not validate in independent replication samples. A GRS including SNPs corresponding to human CKD genes was not significant in an independent subset of cats. Gene-set enrichment and pathway-based analysis (GSEA) was performed for both quantitative phenotypes, with 30 enriched pathways with creatinine. Our results support the utility of GWASs and GSEA for genetic discovery of complex traits in cats, with the caveat of our findings requiring validation.

The new age of renal biomarkers: does SDMA solve all of our problems?

Within clinical small animal practice, diagnosis of both chronic kidney disease and acute kidney injury is common. To assess renal function, measurement of glomerular filtration rate is considered the gold standard. Currently, routine tests of kidney function include surrogate markers of glomerular filtration rate such as serum creatinine, and urea, each with their own limitations, whilst urine protein to creatinine ratio gives an indication of glomerular and tubular handling of protein, and urine specific gravity information about urine concentrating ability by the kidney. These parameters are used together with historical and physical examination data to give a diagnosis of kidney disease following which creatinine, proteinuria and blood pressure are used to stage chronic kidney disease and, together with urine output, grade acute kidney injury according to the International Renal Interest Society. However, there has been much concern that creatinine is insensitive when used to indicate early decline in renal function and this has highlighted the need for additional methods of diagnosing and monitoring these patients, with the potential to allow earlier therapeutic intervention. Symmetric dimethylarginine is a novel biomarker, which has been shown to perform as a surrogate marker of glomerular filtration rate in small animals. This article will review current research on symmetric dimethylarginine and the ways in which it may be utilised in small animal practice; current research supports the use of symmetric dimethylarginine as a screening test for detection of early chronic kidney disease according to International Renal Interest Society guidelines, but further research is required in to the usefulness of symmetric dimethylarginine as a tool for monitoring disease and the effect of non-renal influences.

Occurrence, management and outcome of immune-complex glomerulonephritis in dogs with suspected glomerulopathy in the UK.

OBJECTIVES: To determine the proportion of dogs diagnosed with immune-complex glomerulonephritis in a large cohort of UK dogs with clinical suspicion of glomerular disease in which renal histopathology, including routine light microscopy, transmission electron microscopy and immunofluorescence, had been performed. The second objective was to describe treatment and long-term clinical outcome of dogs diagnosed with immune-complex glomerulonephritis. MATERIALS AND METHODS: Sixty-two UK dogs that underwent renal biopsies for investigation of suspected glomerulopathy (urine protein-to-creatinine ratio persistently >0.5) were included in this retrospective multicentre study. Signalment, clinico-pathological abnormalities, histopathological diagnosis, treatment following diagnosis and survival were recorded. RESULTS: Seventeen (27%) of the dogs with suspected glomerular disease were diagnosed with immune-complex glomerulonephritis and nine (53%) of these were still alive at the study end point, with a median follow-up of 366 days (range 52 to 1299). Six dogs diagnosed with immune-complex glomerulonephritis were treated with mycophenolate. Four received mycophenolate alone for immunosuppression and two received mycophenolate and chlorambucil; all these six dogs were alive at data collection [median follow-up time 712.5 days (range 73 to 1299)]. Seven dogs diagnosed with immune-complex glomerulonephritis did not receive immunosuppressive treatment; only one of these dogs was alive at study end point [median survival time 302 days (range 52 to 723)]. CLINICAL SIGNIFICANCE: Immune-complex glomerulonephritis may be less common in the UK than previously reported in North America and mainland Europe, reducing the likelihood of treatment modification following renal biopsy. Mycophenolate was the most commonly used immunosuppressant for cases of immune-complex glomerulonephritis.

Associations between single nucleotide polymorphisms in the calcium sensing receptor and chronic kidney disease-mineral and bone disorder in cats.

Feline chronic kidney disease (CKD) is associated with high variability in severity of CKD-mineral and bone disorder (CKD-MBD). The calcium sensing receptor (CaSR) regulates circulating parathyroid hormone (PTH) and calcium concentrations. Single nucleotide polymorphisms (SNPs) in the CaSR are associated with severity of secondary renal hyperparathyroidism and total calcium concentrations in human patients receiving haemodialysis. The objective of this study was to explore associations between polymorphisms in the feline CaSR (fCaSR) and biochemical changes observed in CKD-MBD. Client owned cats (≥9years) were retrospectively included. SNP discovery was performed in 20 cats with azotaemic CKD and normal or dysregulated calcium concentrations. Non-pedigree cats (n=192) (125 with azotaemic CKD and 66 healthy), Persians (n=40) and Burmese (n=25) were genotyped for all identified SNPs using KASP. Biochemical parameters from the date of CKD diagnosis or from first visit to the clinic (healthy cats) were used. Associations between genotype and ionized calcium, total calcium, phosphate, PTH and FGF-23 were performed for non-pedigree cats using logistic regression. Sequence alignment against the fCaSR sequence revealed eight novel exonic SNPs. KASP genotyping had high accuracy (99.6%) and a low failure rate (<6%) for all SNPs. Allele frequencies varied between breeds. In non-pedigree cats, one synonymous SNP CaSR:c.1269G>A was associated with logPTH concentration (adjusted for plasma creatinine concentration), with a recessive model having the best fit (G/G vs A/A-G/A, P=0.031). Genetic variation in the fCaSR is unlikely to explain the majority of the variability in presence and severity of CKD-MBD in cats.

Calcitonin Response to Naturally Occurring Ionized Hypercalcemia in Cats with Chronic Kidney Disease.

BACKGROUND: Hypercalcemia is commonly associated with chronic kidney disease (CKD) in cats. OBJECTIVES: To explore the calcitonin response to naturally occurring ionized hypercalcemia in cats with azotemic CKD, and to assess the relationship of plasma calcitonin with ionized calcium, alkaline phosphatase (ALP), and urinary calcium excretion. ANIMALS: Thirty-three client-owned cats with azotemic CKD and ionized hypercalcemia from first opinion practice. METHODS: Cohort study. Calcitonin was measured with an immunoradiometric assay in heparinized plasma. Simple correlations were assessed with Kendall's rank correlation, and the within-subject correlations of calcitonin with ionized calcium and other clinicopathological variables were calculated with a bivariate linear mixed effects model. RESULTS: Calcitonin concentrations above the lower limit of detection (>1.2 pg/mL; range, 1.7-87.2 pg/mL) were observed in 11 of 33 hypercalcemic cats (responders). Blood ionized calcium concentration did not differ significantly between responders (median, 1.59 [1.46, 1.66] mmol/L) and nonresponders (median, 1.48 [1.43, 1.65] mmol/L; P = 0.22). No evidence was found for calcitonin and ionized calcium to correlate between cats (τb = 0.14; P = 0.31; n = 33), but significant positive correlation was evident within individual responders over time (within-subject correlation coefficient [rwithin ], 0.83; 95% confidence interval [CI], 0.63-0.92). Calcitonin correlated negatively over time with plasma ALP (rwithin , -0.55; 95% CI, -0.79 to -0.16). CONCLUSIONS AND CLINICAL IMPORTANCE: Calcitonin does not appear to have an important role in calcium metabolism in cats with CKD.

Plasma N-Terminal Probrain Natriuretic Peptide, Vascular Endothelial Growth Factor, and Cardiac Troponin I as Novel Biomarkers of Hypertensive Disease and Target Organ Damage in Cats.

BACKGROUND: In the absence of ocular target organ damage (ocular-TOD), diagnosis of hypertension is challenging in cats. Biomarkers would provide additional support for the diagnosis of hypertension. HYPOTHESIS: Vascular endothelial growth factor (VEGF), N-terminal probrain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), and urine protein-to-creatinine ratio (UPC) are predictors of systemic hypertension, will be increased in cats with hypertension with or without ocular-TOD, and will decrease with antihypertensive treatment. METHODS: Plasma VEGF, NT-proBNP, and cTnI concentrations and UPC were determined in healthy geriatric cats, normotensive cats with chronic kidney disease (CKD), hypertensive cats with evidence of hypertensive retinopathy (HT-ocular-TOD), and hypertensive cats without hypertensive ocular-TOD (HT-noTOD). Comparisons among groups were performed. Multivariable binary logistic regression models were built to identify independent biomarkers of hypertension and ocular-TOD. Receiver operator characteristic (ROC) curves were drawn to assess clinical use. RESULTS: Cats with HT-ocular-TOD had significantly higher VEGF than all other groups (P < .05) and significantly higher NT-proBNP than healthy cats (P < .001). Healthy cats had significantly lower cTnI than all other groups (P < .05). No differences were found among groups for UPC (P = .08). Cardiac troponin I and VEGF were independent predictors of hypertension (P < .05), but none of the biomarkers were independent predictors of ocular-TOD. N-terminal probrain natriuretic peptide concentrations decreased with antihypertensive treatment (P < .001). The ROC curves indicated that none of the biomarkers met the criteria to function as diagnostic tests for the diagnosis of hypertension or associated ocular-TOD. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Despite statistical significance and changes with ocular-TOD, antihypertensive treatment, or both, VEGF, NT-proBNP, and cTnI did not function as useful diagnostic tests for hypertension. Persistently increased systolic blood pressure (SBP) measurements in combination with fundoscopy remains the preferred method for diagnosis of feline hypertension.

Chronic Kidney Disease in Cats and the Risk of Total Hypercalcemia.

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity in cats with hypercalcemia, but whether CKD is a risk factor for hypercalcemia is unclear. Hypercalcemia often is diagnosed based on total calcium concentration (tCa), which tends to underestimate the ionized calcium concentration (iCa) in cats. OBJECTIVES: Assessment of the performance of tCa for the diagnosis of ionized hypercalcemia, and exploration of factors influencing the relationship between iCa and tCa. Determination of risk factors for incident total hypercalcemia (ie, the development of hypercalcemia based on tCa during follow-up). ANIMALS: Records of a cross-section (n = 477) and observational cohort (n = 367) of client-owned cats with and without azotemic CKD from first opinion practice. METHODS: Retrospective cross-sectional and retrospective cohort study. The diagnostic accuracy of tCa as an index test for ionized hypercalcemia was evaluated, and risk factors for underestimation were explored by binary logistic and linear regression in a cross-section of cats with and without azotemic CKD. Chronic kidney disease and clinicopathological variables were assessed as predictors of incident total hypercalcemia by both time-invariant and time-dependent Cox regression in a cohort of cats. RESULTS: Specificity of tCa for identification of ionized hypercalcemia was high (100%), but sensitivity was low. Underestimation was associated with lower venous bicarbonate concentrations. Cats with CKD had increased risk for incident total hypercalcemia (hazard ratio, 4.29; 95% confidence interval, 1.96-9.37; P < .001). Higher tCa predicted incident total hypercalcemia in both azotemic and nonazotemic cats (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Chronic kidney disease is a risk factor for incident total hypercalcemia, and most cats with increased tCa had concurrent ionized hypercalcemia. Higher baseline tCa predicts incident total hypercalcemia. Prospective studies assessing changes in iCa are warranted.

Nasal infestation by Linguatula serrata in a dog in the UK: a case report.

A two-year-old, female neutered, cross-breed dog imported from Romania was diagnosed with nasal infestation of Linguatula serrata after she sneezed out an adult female. The dog was presented with mucopurulent/sanguinous nasal discharge, marked left-sided exophthalmia, conjunctival hyperaemia and chemosis. Computed tomography and left frontal sinusotomy revealed no further evidence of adult parasites. In addition, there was no evidence of egg shedding in the nasal secretions or faeces. Clinical signs resolved within 48 hours of sinusotomy, and with systemic broad-spectrum antibiotics and non-steroidal anti-inflammatory drugs. Recommendations are given in this report regarding the management and follow-up of this important zoonotic disease.

Factors Influencing the Relationship Between the Dose of Amlodipine Required for Blood Pressure Control and Change in Blood Pressure in Hypertensive Cats.

BACKGROUND: Hypertension is a common problem in elderly cats. In most cats, systolic blood pressure (SBP) of <160 mmHg is achieved in response to amlodipine besylate at either 0.625 or 1.25 mg q24h. The individual cat factors determining dose requirement dose have not been explored. AIMS: To determine whether individual cat factors influence the dose of amlodipine required to achieve adequate blood pressure control and to determine whether factors other than the prescribed dose of drug alter the achieved plasma amlodipine concentrations. METHODS: Fifty-nine hypertensive cats that required 0.625 mg (A) and 41 cats that required 1.25 mg (B) amlodipine to reach a target SBP of <160 mmHg were identified, and plasma amlodipine concentrations were determined. Comparisons were made between groups, and multivariable linear regression models were performed to investigate predictors of antihypertensive response. RESULTS: Cats that required a greater dose of amlodipine had significantly higher SBP at diagnosis of hypertension (A: (median [25th, 75th percentile]) 182 [175,192] mmHg; B: 207 [194,217] mmHg, P < .001), but comparable blood pressure was achieved after treatment. Plasma amlodipine concentrations were directly related to the dose of amlodipine administered. At diagnosis, cats in group B had significantly lower plasma potassium concentration (A: 4.1 [3.8,4.5]; B: 3.8 [3.6,4.2] mEq/L, P < .01). Weight did not differ between groups. The decrease in SBP was directly and independently associated with the SBP at diagnosis and the plasma amlodipine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with higher blood pressure at diagnosis might require a greater dose of amlodipine to control their blood pressure adequately. Differences in amlodipine pharmacokinetics between cats do not seem to play a role in the antihypertensive response.

Uromodulin gene variants and their association with renal function and blood pressure in cats: a pilot study.

OBJECTIVES: In humans, genome-wide association studies have identified variants in the uromodulin gene (UMOD) associated with blood pressure and renal function. This study aimed to evaluate the association of single nucleotide polymorphisms at the UMOD locus with renal function and blood pressure in cats. METHODS: We retrospectively identified cats aged 14 years that had participated in a geriatric monitoring program, and from which stored DNA samples were available, from a computerised database. We then measured the association of specific single nucleotide polymorphisms in the feline UMOD gene with renal function and systolic blood pressure as continuous variables and, also, the dichotomous outcome of azotaemic chronic kidney disease and systemic hypertension. RESULTS: Eight intronic single nucleotide polymorphisms, one 1372 base pairs upstream from UMOD and two exonic single nucleotide polymorphisms were evaluated in 227 cats with renal and blood pressure data. An analysis of 188 cats found four single nucleotide polymorphisms to be significantly associated (P<0·01) with systolic blood pressure although all were in linkage disequilibrium. No significant associations were identified between single nucleotide polymorphisms and renal function or chronic kidney disease. CLINICAL SIGNIFICANCE: Results of this pilot study suggest that genetic variation in UMOD might influence blood pressure in cats, similar to findings in humans. Validation of these results is required.

Psychometric Validation of a General Health Quality of Life Tool for Cats Used to Compare Healthy Cats and Cats with Chronic Kidney Disease.

BACKGROUND: Numerous validated psychometric tools are available to assess impact of disease on a human's quality of life (QoL). To date, no psychometrically validated general health-related QoL tool exists for cats. HYPOTHESIS/OBJECTIVES: To develop and validate a tool for assessment of owner-perceived QoL in cats (CatQoL) and to use this tool to compare QoL between healthy cats and those with chronic kidney disease (CKD). ANIMALS/SUBJECTS: Total of 204 owners of young healthy cats (YH, n = 99; <9 years), older healthy cats (OH, n = 35), and cats diagnosed with CKD (CKD, n = 70) completed the CatQoL. METHODS: Discussions with a focus group and 2 pilot surveys informed design of 16 QoL questions grouped into 4 domains. Each item scored according to frequency and importance, and item-weighted-impact-scores were calculated. The validity of the tool was assessed using principal components analysis and Cronbach's α. The average item-weighted-impact-score (AWIS) was compared among groups and domains. RESULTS: Sixteen-item CatQoL showed good internal consistency reliability (Cronbach's α, 0.77) and unidimensionality with significant loadings (0.2-0.7) and communalities (>0.3). Young healthy cats had significantly higher AWIS (median [IQR], 1.25 [0.63, 1.88]) than OH (0.56 [-0.06, 1.00]) and CKD cats (-0.06 [-0.81, 0.88]), P < .001). CKD cats had significantly lower AWIS for eating domain (YH: 2.00 [1.00, 3.00]; OH: 2.00 [0.67, 3.00]; CKD : 1.00 [0.00, 2.67]) when compared with the YH group and OH group, and all groups differed significantly in their management domain (YH: -0.50 [-1.00, 0.00]; OH: -1.00 [-1.88, -0.50]; CKD : -1.50 [-2.50, -1.00], P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The CatQoL was validated for use in cats, and can be used as additional assessment parameter in clinical and research settings.

Changes in systolic blood pressure over time in healthy cats and cats with chronic kidney disease.

BACKGROUND: Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross-sectional studies have suggested that blood pressure in cats increases with age. HYPOTHESIS/OBJECTIVES: To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension. ANIMALS/SUBJECTS: Two hundred and sixty-five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified. METHODS: Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive [NT] or developed hypertension [DH]): Healthy-NT, Healthy-DH, CKD-NT and CKD-DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined. RESULTS: Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty-seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension. CONCLUSIONS AND CLINICAL IMPORTANCE: The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD.

Plasma renin activity and aldosterone concentrations in hypertensive cats with and without azotemia and in response to treatment with amlodipine besylate.

BACKGROUND: Role of renin-angiotensin aldosterone system (RAAS) in feline systemic hypertension is poorly understood. OBJECTIVES: Examine plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) in normotensive and hypertensive cats with variable renal function and in response to antihypertensive therapy. ANIMALS: One hundred and ninety-six cats >9 years from first opinion practice. METHODS: PRA, PAC, and aldosterone-to-renin ratio (ARR) were evaluated in cats recruited prospectively and grouped according to systolic blood pressure (SBP) and renal function (nonazotemic normotensive [Non-Azo-NT], nonazotemic hypertensive [Non-Azo-HT], azotemic normotensive [Azo-NT], azotemic hypertensive [Azo-HT]). Changes in PRA and PAC were evaluated with antihypertensive therapy (amlodipine besylate). RESULTS: Plasma renin activity (ng/mL/h; P = .0013), PAC (pg/mL; P < .001), and ARR (P = 0.0062) differed significantly among groups. PRA (ng/mL/h) was significantly lower in hypertensive (Non-Azo-HT; n = 25, median 0.22 [25th percentile 0.09, 75th percentile 0.39], Azo-HT; n = 44, 0.33 [0.15, 0.48]) compared with Non-Azo-NT cats (n = 57, 0.52 [0.28, 1.02]). Azo-HT cats had significantly higher PAC (n = 22, 149.8 [103.1, 228.7]) than normotensive cats (Non-Azo-NT; n = 26, 45.4 [19.6, 65.0], Azo-NT; n = 18, 84.1 [38.6, 137.8]). ARR was significantly higher in Azo-HT (n = 20, 503.8 [298.8, 1511]) than Azo-NT cats (n = 16, 97.8 [77.0, 496.4]). Significant increase in PRA was documented with antihypertensive therapy (pretreatment [n = 20] 0.32 [0.15-0.46], posttreatment 0.54 [0.28, 1.51]), but PAC did not change. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypertensive cats demonstrate significantly increased PAC with decreased PRA. PRA significantly increases with antihypertensive therapy. Additional work is required to determine the role of plasma aldosterone concentration in the pathogenesis of hypertension and whether this relates to autonomous production or activation of RAAS without demonstrable increase in PRA.

Evaluation of predictors of the development of azotemia in cats.

BACKGROUND: Chronic kidney disease (CKD) is a common condition in geriatric cats. Diagnosis is based on the development of persistent azotemia with inadequate urine concentrating ability. Biomarkers are sought for early identification. HYPOTHESIS: Clinical variables, urine concentrating ability, proteinuria, and N-acetyl-beta-D-glucosaminidase (NAG) index will be predictive of cats at risk of developing azotemia within 12 months. ANIMALS: Client-owned nonazotemic geriatric (>or=9 years) cats. METHODS: Prospective longitudinal cohort study monitoring a population of healthy nonazotemic geriatric cats every 6 months until development of azotemia, death, or the study end point (September 30, 2007). Multivariable logistic regression analysis was used to assess baseline clinical, biochemical, and urinalysis variables, urine protein to creatinine ratio (UP/C), urine albumin to creatinine (UA/C) ratio, and urinary NAG index as predictors of development of azotemia. RESULTS: One hundred and eighteen cats were recruited with a median age of 13 years. Ninety-five cats (80.5%) had been followed or reached the study end point by 12 months of which 30.5% (29/95) developed azotemia. Age, systolic blood pressure, plasma creatinine concentration, urine specific gravity, UP/C, UA/C, and NAG index were significantly associated with development of azotemia in the univariable analysis (P

Plasma asymmetric dimethylarginine, symmetric dimethylarginine, l-arginine, and nitrite/nitrate concentrations in cats with chronic kidney disease and hypertension.

BACKGROUND: Chronic kidney disease (CKD) and hypertension have been associated with decreased bioavailability of nitric oxide (NO) and endothelial dysfunction. Increased concentrations of the endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) are implicated. HYPOTHESIS: Plasma ADMA concentration is increased in cats with CKD and systemic hypertension corresponding to a decrease in total plasma nitrate/nitrite (NOx) availability. Decrease in systolic blood pressure (SBP) and proteinuria during treatment of hypertension with amlodipine besylate may be associated with increased NOx availability. ANIMALS: Sixty-nine client-owned normotensive and hypertensive cats with variable azotemia. METHODS: Plasma ADMA, symmetric dimethylarginine (SDMA), and l-arginine were measured simultaneously by hydrophilic-interaction liquid chromatography-electrospray tandem mass spectrometry in cats from 6 groups: normotensive nonazotemic (n = 10), normotensive mildly azotemic (n = 10), hypertensive mildly azotemic with hypertensive retinopathy (n = 20), hypertensive mildly azotemic without hypertensive retinopathy (n = 10), normotensive moderately azotemic cats (n = 10), and hypertensive nonazotemic cats (n = 9). Plasma NOx concentrations were measured. RESULTS: A moderate correlation between plasma creatinine and ADMA (n = 69, r= .608, P < .001), SDMA (n = 69, r= .741, P < .001), and NOx concentrations (n = 69, r= .589, P < .001) was observed. There was no association among plasma ADMA, SDMA, and NOx concentrations and SBP. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma ADMA and SDMA concentrations are increased in cats with CKD and correlate with plasma creatinine concentration. This may imply the presence of endothelial dysfunction in cats with CKD. Plasma ADMA concentrations were not associated with systemic hypertension. Treatment of systemic hypertension with amlodipine besylate did not affect plasma ADMA or NOx concentrations.